Successful treatment of severe ARDS caused by accidental inhalation of nitric acid fumes with veno-venous ECMO: A case report and literature review

Rationale: The treatment of severe acute respiratory distress syndrome caused by accidental inhalation of nitric acid fumes is challenging. Few successful cases have been reported in literature. Owing to the development of extracorporeal life support, extracorporeal membrane oxygenation (ECMO) may play an important role in treatment. Patient concerns: A 40-year-old man was accidentally exposed to nitric acid fumes for 10 minutes in a factory. Mild throat irritation and dyspnea occurred 3.5 hours after exposure. Severe dyspnea recurred approximately two hours later. Chest computed tomography revealed bilateral interstitial edema. Tracheal intubation and mechanical ventilation were provided when the non-invasive ventilator failed to support the patient. However, his vital signs, respiratory function, and circulation were aggravated. Diagnosis: Aspiration pneumonia (inhalation of nitric acid fumes), acute respiratory distress syndrome, and hypertension. Interventions: Veno-venous ECMO (VV-ECMO) was started 6 hours after exposure at the intensive care unit. During VV-ECMO, hypoxia improved. However, chest radiography revealed aggravated pulmonary edema. Prone positioning under ultrasound monitoring and high-dose methylprednisolone were administered on the first day. Nebulization and fiberoptic bronchoscopy for airway management were performed on the second day after the exposure. Pulmonary secretions were significantly reduced 48 hours later. Outcomes: The patient was weaned off V-V ECMO after 6 days, achieved the standard of extubation after 9 days, and was discharged without serious pulmonary or infectious complications after 12 days of hospitalization. Three weeks after discharge, the patient’s lung function showed a slight decline in the diffusion function. Two months after discharge, the patient’s lung function returned to normal. Lesson: Early ECMO combined with prone positioning and visualized management through ultrasonography can better improve the prognoses of patients and promote lung function recovery.


Introduction
Nitric acid is a strong oxidizing agent. Leakage of nitric acid occasionally occurs. The inhalation of nitric acid fumes can lead to toxic pulmonary edema. However, little evidence has been provided regarding the treatment of diseases caused by accidental inhalation of nitric acid fumes. [1,2] Here, we report a healed case of nitric acid fume poisoning with veno-venous extracorporeal membrane oxygenation (VV-ECMO) treatment at an early time point after exposure and in a prone position (PP) during V-V ECMO treatment.

Case report
A 40-year-old man was admitted to the emergency department of our hospital because of accidental exposure to nitric acid fumes for 10 minutes in a factory. The industrial gas was Medicine composed of four volumes of 65% nitric acid. Mild throat irritation and dyspnea occurred 3.5 hours after exposure. Approximately 2 hours later, the severe dyspnea recurred. A noninvasive ventilator with breathing parameters (FiO 2 50%; Pi, 14; Ps, 6) was provided 12 hours after exposure. However, the oxygenation was not maintained. Tracheal intubation was performed 24 hours after exposure. However, even when high-level ventilator support was administered, the respiratory function deteriorated rapidly. Thus, VV-ECMO was used in the intensive care unit. The pre-ECMO survival probability was calculated using respiratory ECMO. The APACHE II score was 30.
The sequence of events for patients supported by V-V ECMO is outlined in the following paragraphs.
Exposure time (ET): Incident occurred. The patient was exposed to fumes of nitric acid for approximately 10 minutes. He had dry coughing and a feeling of suffocation for a very short period. At that time, no eye, nasal, or skin irritation was observed.
Four hours after ET, the patient experienced paroxysms of cough and shortness of breath. The patient was admitted to the emergency department of a local hospital. Chest computed tomography performed at a local hospital revealed bilateral interstitial edema (Fig. 1).
Twelve hours after ET, the patient was sent to the emergency department of our hospital with moderate-to-severe respiratory distress. Physical examination revealed a temperature of 38.5°C, respiratory rate of 45 breaths per minute, blood pressure of 145/85 mm Hg, and pulse of 136 beats/ min. Room air oxygen saturation was 80%. Noninvasive ventilation was initiated immediately.
24 hours after ET, the FiO 2 of noninvasive ventilation was rapidly adjusted to 100% to maintain oxygen saturation. The arterial blood gas showed a pH of 7.32 (7.35-7.45), PaCO 2 of 29 mm Hg (35-45 mm Hg), PaO 2 of 56 mm Hg (75-100 mm Hg), and bicarbonate of 15 mmol/L (21-27 mmol/L), indicating that the patient was rapidly deteriorating into respiratory failure. The patient was intubated emergently, accompanied by continuous neuromuscular blockade. Methylprednisolone (200 mg) nebulized with bronchodilators, N-acetylcysteine, and sivelestat sodium were administered. Two hours after intubation, the patient's respiratory condition worsened. Mechanical ventilation with positive end-expiratory pressure (PEEP) was used. Catecholamines were also administered (Norepinephrine 0.5 μg/kg/ min). 30 hours after ET: Because of the persistent worsening of respiratory situation (pH 7.23, PaCO 2 78 cmH 2 O, PaO 2 52 cmH 2 O), inverse ratio ventilation (I:E 2:1, PEEP 10 cmH 2 O, FIO 2 1.0) was installed. Chest radiography revealed diffuse infiltration throughout all the lung fields ( Fig. 2A). The decision was made to place the patient on a twin pulse extracorporeal life support system (BE-PLS: Maquet). A 17-F arterial and 21-F venous catheter were inserted into the femoral artery and vein percutaneously using a modified Seldinger method with visualization critical ultrasound. V-V ECMO was set to 2.5 a blood flow/min with an oxygen flow of 1.5 L/min. This resulted in the enhancement of oxygen for the next 6 hours and the continuous elimination of CO 2 . During the initial application of V-V ECMO, the blood pressure was 114/62 mm Hg and the heart rate was 92 bpm.
Subsequently, the patient required both V-V ECMO and PP for 12 hours per day for the next 4 days. A tracheal electronic endoscope was used to remove secretions and bronchoalveolar lavage fluid.
Day 5: The weaning process was started after successful improvement of lung function (FiO 2 0.3, PEEP 8 cmH 2 O, plateau pressure Pplat 17 cmH 2 O). Radiography showed that the diffuse plaques and infiltration in all lung fields were reduced, and the costophrenic angle in the left region was blunt (Fig. 2B).
Day 6: Extracorporeal blood flow was reduced stepwise to 1.5 L/min. The gas flow was tapered mostly parallel to the blood flow and finally shut off for 1 hours. The patient did not present with dyspnea or tachypnea. The V-V ECMO was successfully weaned off V-V ECMO.
Day 8: The mechanical ventilation was withdrawn. Day 9: The patient was transferred to the respiratory department.
Day 11: The patient was discharged from the hospital. The laboratory results of patients at different time points are shown in Table 1.
Two months after discharge, the patient's lung function returned to normal ( Table 2).

Discussion
Inhalation of nitric acid fumes leads to toxic pulmonary edema, which can be caused by strong stimulation of and corrosive effects on lung tissue. [3] The fumes can damage the surfactant substances and capillary wall permeability of the lung, resulting in the enhancement of alveolar wall permeability, which could cause the body fluids in the capillaries to permeate into the lung interstitium and alveoli. [4] In addition, the excitement of synthetic nerves can cause spasms of the right total lymphatic tube, resulting in a disordered lymphatic reflux. Subsequently, acute lung injury occurs. [2]  Based on a search of PubMed in June 2021, we reviewed all papers using the terms 'nitric acid fume inhalation, nitric acid inhalation AND accident, nitric acid inhalation, nitric acid inhalation AND toxic, nitric acid AND corticosteroids,'and 'nitric acid AND ECMO'. Based on the references in these articles, we found additional papers on these topics. Sixteen cases of inhalation injury to nitric acid fumes were reported in ten articles (Table 3). [1,[3][4][5][6][7][8][9][10][11] Fourteen patients' exposures were related to industrial work. Two other cases were exposed during farmer work and leisure cleaning. In industrial work-related exposures, four patients were intoxicated during tank cleaning activities performed without respiratory protection. There were 6 severe acute respiratory distress syndrome (ARDS) cases among the 16 exposed patients. Of the 6 patients with severe ARDS, four died. ECMO was used in two surviving patients.     Shin et al reported that patients who were treated early with ECMO combined with N-acetylcysteine after nitric acid inhalation were weaned from ECMO after 8 days and discharged normally after 18 days in 2007. [1] Lee et al reported a patient who was weaned from ECMO for 7 days and discharged without complications in 2014. [4] In our case, lung compliance and oxygenation were significantly improved on the fifth day, ECMO was withdrawn at 7 days, and the patient was discharged successfully on the 12th day. The pulmonary function was slightly limited. Two months after discharge, the patient's lung function returned to normal. The use of early extracorporeal life support before the aggravation of tissue hypoxia is very important in patients with inhalation lung injury. [12] Some studies have suggested that PP treatment with VV-ECMO support should be considered in these patients. [13,14] PP can not only can promote sputum drainage, especially in chemical inhalation pneumonia, but also can avoid gravity dependent zone atelectasis. By improving oxygenation, hemodynamics can expedite weaning. [15,16] The use of PP is an important reason for the rapid withdrawal of ECMO in this patient. This phenomenon has not been reported previously.
Another important method in the treatment of the patient was visualized management using ultrasound. Critical ultrasound has transformed ECMO from technology to precise management. [17,18] Extracorporeal Life Support Organization showed that ultrasound was mandatory during the initiation of ECMO. Cannula insertion, hemodynamics, monitoring, and detection of complications can be assisted with ultrasound to shorten the operation time of ECMO. [19] Left room pressure, monitoring of lung B-line conditions, and dynamic adjustment of patient capacity were assisted by ultrasound. In our case, the chest radiograph showed rapid improvement in pulmonary edema, depending on dynamic cardiopulmonary ultrasound assessment. We recommend visualizing critical ultrasound intervention in the management of all ECMO patients to avoid inappropriate interventions and achieve better implementation of precision treatment.

Conclusion
Severe ARDS caused by nitric acid inhalation is rarely associated with inhalation pneumonia. Early ECMO combined with PP and visualized management through ultrasonography can improve the prognosis of patients and promote lung function recovery.